Publishing type：Research paper (scientific journal)  

DOI： 10.3390/BIOMEDICINES12051011

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

<jats:title>Abstract</jats:title><jats:p>Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta‐4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of <jats:italic>GJB4</jats:italic> transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of <jats:italic>GJB4</jats:italic> in cultured pancreatic cancer cells resulted in G<jats:sub>0</jats:sub>/G<jats:sub>1</jats:sub> arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of <jats:italic>GJB4</jats:italic> accelerated cell proliferation, migration, and invasion in a SUIT‐2 cell line, whereas MET inhibitor canceled the acceleration. <jats:italic>GJB4</jats:italic> suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET–AKT activities. Such data suggest that targeting the GJB4–MET axis could represent a promising new therapeutic strategy for pancreatic cancer.</jats:p>

DOI： 10.1111/cas.16101

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Language：English   Publishing type：Research paper (scientific journal)  

<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan.</jats:p>
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<jats:sec>
<jats:title>Methods &amp; Results</jats:title>
<jats:p>In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0–9.2).</jats:p>
</jats:sec>
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<jats:title>Conclusions</jats:title>
<jats:p>The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.</jats:p>
<jats:p>An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.</jats:p>
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DOI： 10.1093/jjco/hyad131

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Publishing type：Research paper (scientific journal)  

Web of Science

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Publishing type：Research paper (scientific journal)  

Web of Science

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11280/gee.65.244

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.7741-21

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11405/nisshoshi.118.874

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